Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, Netherlands
Department of Clinical Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
BMJ. 2021 Nov 29;375:e066306. doi: 10.1136/bmj-2021-066306.
To identify the optimal estimated glomerular filtration rate (eGFR) at which to initiate dialysis in people with advanced chronic kidney disease.
Nationwide observational cohort study.
National Swedish Renal Registry of patients referred to nephrologists.
Patients had a baseline eGFR between 10 and 20 mL/min/1.73 m and were included between 1 January 2007 and 31 December 2016, with follow-up until 1 June 2017.
The strict design criteria of a clinical trial were mimicked by using the cloning, censoring, and weighting method to eliminate immortal time bias, lead time bias, and survivor bias. A dynamic marginal structural model was used to estimate adjusted hazard ratios and absolute risks for five year all cause mortality and major adverse cardiovascular events (composite of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) for 15 dialysis initiation strategies with eGFR values between 4 and 19 mL/min/1.73 m in increments of 1 mL/min/1.73 m. An eGFR between 6 and 7 mL/min/1.73 m (eGFR) was taken as the reference.
Among 10 290 incident patients with advanced chronic kidney disease (median age 73 years; 3739 (36%) women; median eGFR 16.8 mL/min/1.73 m), 3822 started dialysis, 4160 died, and 2446 had a major adverse cardiovascular event. A parabolic relation was observed for mortality, with the lowest risk for eGFR. Compared with dialysis initiation at eGFR, initiation at eGFR was associated with a 5.1% (95% confidence interval 2.5% to 6.9%) lower absolute five year mortality risk and 2.9% (0.2% to 5.5%) lower risk of a major adverse cardiovascular event, corresponding to hazard ratios of 0.89 (95% confidence interval 0.87 to 0.92) and 0.94 (0.91 to 0.98), respectively. This 5.1% absolute risk difference corresponded to a mean postponement of death of 1.6 months over five years of follow-up. However, dialysis would need to be started four years earlier. When emulating the intended strategies of the Initiating Dialysis Early and Late (IDEAL) trial (eGFR eGFR) and the achieved eGFRs in IDEAL (eGFR eGFR), hazard ratios for all cause mortality were 0.96 (0.94 to 0.99) and 0.97 (0.94 to 1.00), respectively, which are congruent with the findings of the randomised IDEAL trial.
Very early initiation of dialysis was associated with a modest reduction in mortality and cardiovascular events. For most patients, such a reduction may not outweigh the burden of a substantially longer period spent on dialysis.
确定开始透析的最佳估算肾小球滤过率（eGFR），适用于晚期慢性肾脏病患者。
全国性观察性队列研究。
国家瑞典肾脏登记处，患者转介给肾脏科医生。
患者基线 eGFR 为 10-20mL/min/1.73m，并于 2007 年 1 月 1 日至 2016 年 12 月 31 日期间入组，随访至 2017 年 6 月 1 日。
使用克隆、删失和加权方法模拟临床试验的严格设计标准，消除永生时间偏倚、领先时间偏倚和幸存者偏倚。使用动态边际结构模型，估算 15 种 eGFR 起始策略的调整风险比和绝对风险，eGFR 起始策略范围为 4-19mL/min/1.73m，以 1mL/min/1.73m 为增量。以 eGFR 6-7mL/min/1.73m（eGFR）为参考。
在 10290 例晚期慢性肾脏病（中位年龄 73 岁；3739 例（36%）女性；中位 eGFR 16.8mL/min/1.73m）的患者中，有 3822 例开始透析，4160 例死亡，2446 例发生主要不良心血管事件。死亡率呈抛物线关系，eGFR 最低风险最低。与 eGFR 时开始透析相比，eGFR 时开始透析的患者，五年死亡率绝对风险降低 5.1%（95%置信区间 2.5%至 6.9%），主要不良心血管事件风险降低 2.9%（0.2%至 5.5%），相应的风险比为 0.89（95%置信区间 0.87 至 0.92）和 0.94（0.91 至 0.98）。这 5.1%的绝对风险差异相当于五年随访期间平均推迟死亡 1.6 个月。然而，需要提前四年开始透析。当模拟早期和晚期启动透析的 IDEAL 试验（eGFR）的预期策略（eGFR 时开始透析）和 IDEAL 中实现的 eGFR（eGFR 时开始透析）时，全因死亡率的风险比分别为 0.96（0.94 至 0.99）和 0.97（0.94 至 1.00），与随机 IDEAL 试验的结果一致。
非常早期开始透析与死亡率和心血管事件的适度降低相关。对于大多数患者来说，这种降低可能不会超过透析时间显著延长的负担。
